The impact of the SARS‐CoV‐2 pandemic on global influenza surveillance: Insights from 18 National Influenza Centers based on a survey conducted between November 2021 and March 2022

Abstract Background National Influenza Centers (NICs) have played a crucial role in the surveillance of SARS‐CoV‐2. The FluCov project, covering 22 countries, was initiated to monitor the impact of the SARS‐CoV‐2 pandemic on influenza activity. Methods This project consisted of an epidemiological bulletin and NIC survey. The survey, designed to assess the impact of the pandemic on the influenza surveillance system, was shared with 36 NICs located across 22 countries. NICs were invited to reply between November 2021 and March 2022. Results We received 18 responses from NICs in 14 countries. Most NICs (76%) indicated that the number of samples tested for influenza decreased. Yet, many NICs (60%) were able to increase their laboratory testing capacity and the “robustness” (e.g., number of sentinel sites) (59%) of their surveillance systems. In addition, sample sources (e.g., hospital or outpatient setting) shifted. All NICs reported a higher burden of work following the onset of the pandemic, with some NICs hiring additional staff or partial outsourcing to other institutes or departments. Many NICs anticipate the future integration of SARS‐CoV‐2 surveillance into the existing respiratory surveillance system. Discussion The survey shows the profound impact of SARS‐CoV‐2 on national influenza surveillance in the first 27 months of the pandemic. Surveillance activities were temporarily disrupted, whilst priority was given to SARS‐CoV‐2. However, most NICs have shown rapid adaptive capacity underlining the importance of strong national influenza surveillance systems. These developments have the potential to benefit global respiratory surveillance in the years to come; however, questions about sustainability remain.

Discussion: The survey shows the profound impact of SARS-CoV-2 on national influenza surveillance in the first 27 months of the pandemic. Surveillance activities were temporarily disrupted, whilst priority was given to SARS-CoV-2. However, most NICs have shown rapid adaptive capacity underlining the importance of strong national influenza surveillance systems. These developments have the potential to benefit global respiratory surveillance in the years to come; however, questions about sustainability remain. The emergence of a new respiratory infection  in early 2020 has had a profound impact on the activity and surveillance of other respiratory infections including influenza. 1 Influenza causes seasonal epidemics in most parts of the world and is responsible for a high burden of disease. [2][3][4] In temperate climates, influenza activity generally peaks in colder, winter months. However, during the Northern Hemisphere's winter of 2019/2020, seasonal influenza activity was dramatically interrupted with limited to no activity reported in most countries in both hemispheres. 1,5,6 In contrast, during the Southern Hemisphere winter of 2021 and Northern Hemisphere winter of 2021/2022, many countries saw co-circulation of both SARS-CoV-2 and influenza. However, the levels of influenza activity during winter remained far lower compared with pre-COVID years. 6 Yet, several countries (e.g., France and South Africa) experienced a second wave of influenza activity outside of the typical influenza season. 7 High levels of influenza activity returned for several Southern Hemisphere countries in 2022 with Australia experiencing higher weekly case counts compared with the 5-year average. 8,9 A variety of factors are thought to have contributed to these unusual patterns of influenza activity. These include the introduction and/or relaxation of nonpharmaceutical interventions (NPIs), such as travel regulations, mask wearing, viral interference as well as high (er) influenza vaccination rates, and changes in care-seeking behavior or patient pathways. [10][11][12][13][14] The "Global Influenza Surveillance and Response System" (GISRS), managed by the World Health Organization (WHO), is the primary global mechanism and resource for the surveillance and control of influenza. 15,16 This system was established in 1952, celebrating its 70th birthday in 2022, and currently encompasses 146 National Influenza Centers (NICs) based in 123 countries. 17,18 NICs play a critical role in pandemic influenza risk assessment and the WHO recommendations for the influenza vaccine composition by conducting and sharing surveillance data to the FluNet platform. 16,19,20 FluNet is a dataset that provides publicly available, national level, weekly influenza surveillance data. All NICs adhere to common protocols/ regulations and are periodically evaluated. Yet, major differences in the characteristics of their surveillance system exist (e.g., geographical representativeness or case definitions). These differences can impact the quality and representativeness of data reported to FluNet. 21 In addition, the reliability, completeness, and accuracy of the influenza surveillance data are largely driven by national healthcare infrastructures and appear positively associated with a higher number of NICs as well as participating (sentinel) sites and greater health expenditures. 22 Since the beginning of the pandemic, these national influenza surveillance systems have been leveraged for the surveillance of the SARS-CoV-2 virus. 20 As a result, many NICs became COVID-19 testing centers that functioned alongside national public, and private sector COVID-19-specific testing centers. 23 To monitor the impact of the SARS-CoV-2 pandemic on influenza activity and surveillance, the Flu-CoV project (nivel.nl/en/flucov) was initiated in 2021. As part of this project, we published a monthly epidemiological bulletin portraying SARS-CoV-2 activity alongside influenza in 22 countries around the world. In addition, the project consisted of a survey to be circulated digitally among NICs located in the countries portrayed in the bulletin.
The survey aimed to increase our understanding of national influenza surveillance structures and how these were affected by the COVID-19 pandemic. Here, we present the influenza surveillance data we retrieved as part of the FluCov project in combination with the survey outcomes and discuss the overall impact the pandemic has had on influenza surveillance including the quality of surveillance data and the likely future of influenza surveillance. These bulletins have been published since June 2021 and provide an overview of the number of positive cases of influenza and SARS-CoV-2 and the percentage of specimens testing positive from January 2019 onwards. 6 The current paper focuses only on the influenza surveillance data extracted as part of this project in combination with the NIC survey.

| Surveillance data extraction
Influenza data on weekly case numbers and number of specimens taken were extracted from FluNet. 24 The data are provided by NICs and other national influenza reference laboratories collaborating actively with GISRS or are uploaded from WHO regional databases.
Data were extracted from the FluNet platform at the beginning of each month since June 2021, and historical data were extracted from the 1st of January 2019 onwards. Data from this platform are regularly updated and sometimes retrospectively corrected.

| National Influenza Centers survey
To better understand (evolution of) the surveillance data reported by the NICs during the pandemic, we designed a survey to be filled out by a NIC representative (see Supporting Information) using surveyplanet.com. 25 The survey consisted of two parts to be filled out (a) by those who report influenza surveillance data to the FluNet platform or (b) by those who report SARS-CoV-2 surveillance data to the WHO. A draft version of the survey was reviewed by two NIC collaborators as well as shared with the Global Influenza Program team at the WHO for feedback after which we incorporated their suggestions.
NICs were invited to reply to the survey between November 2021 and March 2022. Contact details for NIC contact persons were retrieved by internet searches. If a provided answer was unclear, we retrospectively contacted the participating NIC for clarification.
Survey results were agreed to be treated confidentially and are thus reported as aggregated responses (i.e., data are not presented by country).    being tested for influenza since the start of the pandemic was reduced, and nine of those reported a reduction of ≥50% ( Figure 3).

| Survey results
Of the countries reporting an increase in samples tested for influenza (24%, 4/17), one reported an increase of ≥50%, one between 25% and 50%, one between 10% and 25%, and one reported an increase of 0%-10%. Responses from NICs in LMIC did not differ with 66% (4/6) reporting a decrease in the number of samples tested for influenza, of which three reported that this was a reduction of ≥50%.
Even before the COVID-19 pandemic, the sources (e.g., hospitalized care or general practitioners [GP]) of samples to be tested for influenza uploaded onto FluNet per country varied widely (Table S1). Following the COVID-19 pandemic onset, most NICs (n = 14) saw a shift in sample origin, with only two NICs (see responses 8 and 14; Table S1) reporting no shifts in surveillance sample sources. No distinct pattern in these shifts could be identified.
Whereas some NICs report that the majority source of samples shifted toward the hospital setting, others reported that the majority of samples were now taken from the outpatient setting or a different distribution all together.
The majority (59%, 10/17) of NICs reported that their influenza system has been "structurally" changed since the start of the pandemic; this proportion was similar in HICs (55%, 6/11) and LMICs in the near future. One of the NICs indicated that the sustainability of the increased number of laboratories with sequencing capacity will be a challenge for the future. Another NIC indicated that the genomic surveillance of SARS-CoV-2 has enabled them to conduct faster genome sequencing and improved bioinformatics analysis for public health action, processes that they plan to apply to the analysis of influenza surveillance data as well.  Table S2.

| DISCUSSION
The SARS-CoV-2 pandemic has had a profound impact on influenza activity as well as the national and global influenza surveillance system. 6,29,30 In line with other literature, the FluCov epidemiological bulletins showed how the timing and intensity of influenza activity were atypical and often limited between 2020 and 2022. 6 Yet our survey results also indicate that many NICs saw a substantial reduction in the number of specimens being tested for influenza since the start of the pandemic. Although this decrease likely also resulted from ongoing low rates of influenza circulation, 29 it suggests that for many NICs, the surveillance of influenza was (temporarily) halted or disrupted, whilst priority was given to the SARS-CoV-2 pandemic.

| Impact of SARS-CoV-2 pandemic on national surveillance data
The NICs play a crucial role in the surveillance of influenza at a national level, and this involves many different activities such as the testing of samples, performing strain characterizations, providing specimens to the WHO reference laboratories for the vaccine strain selection procedure, writing national surveillance bulletins, and carrying out or supporting research projects. 17 Our survey shows how these national systems differed greatly across countries prior to the SARS-CoV-2 pandemic and that surveillance activities were variously disrupted as a consequence of the pandemic response efforts. We found that the sources of samples, the geographic and demographic representatives, and the diagnostic methods differed. All of these factors were also impacted by the pan- This means that the lower influenza case counts, albeit largely caused by limited influenza circulation, could have also been caused by changes in the structure of the surveillance system 33 or decreases in syndromic consultations. 1 These factors should be considered when interpreting influenza surveillance data that were collected during the SARS-CoV-2 pandemic and may affect the reliability of the data presented through FluNet.

| Strengthening the influenza surveillance systems since the emergence of SARS-CoV-2
Though the influenza surveillance systems appeared to have been disrupted in the majority of NICs, in most instances, the structural changes that are reported have the potential to benefit influenza surveillance in the long term. 36 The majority of NICs reported an increase in the capacity of samples that they can now test for influenza and 70% reported an increase in "robustness." This robustness takes several forms among which are increased geographical representatives, increased number of sentinel sites, and increased availability of funding for equipment and personnel. In addition, we found an increased availability of PCR testing, the importance of which was underlined by the pandemic.
The roll-out of additional reporting systems, increases in sentinel sites, and better geographic representativeness as a result of the SARS-CoV-2 pandemic have the potential to help provide a better picture of the epidemiology and overall burden of influenza at a national level in the future. 36 The increased availability of PCR testing, including multiplex testing, will also aid this and could assist in creating improved recommendations for influenza and likely SARS-CoV-2 vaccine antigen recommendations. It should be noted that despite increasing our understanding of the epidemiology of influenza, these changes are likely to also affect the historical comparability of the data and have possibly increased the sensitivity of surveillance for other respiratory pathogens, changes that are important to be aware of for future interpretation of these different data sources (e.g., epidemic thresholds).
Our results show how NICs were able to scale up and repurpose resources (e.g., staff and equipment) following the start of the SARS-CoV-2 pandemic. Their ability to do so and respond to a new pathogen threat highlights the importance of strong national influenza surveillance systems globally. 37 Currently, NICs are located in approximately 60% of WHO member states, 19 and not all regions and populations are equally represented with only 16 NICs located in the WHO Africa region compared with 54 in the WHO Europe region. 17 This leaves gaps in knowledge as well as an opportunity to increase global pandemic preparedness. Though our results did not show many discrepancies between the way in which surveillance in HICs was impacted by the pandemic compared with LMICs, the latter are known to have lower quality surveillance data. 22 As such, it is important to continue efforts to strengthen these systems.

| The future of global influenza surveillance
With SARS-CoV-2 being likely to continue to circulate, 38

| Limitations
Our study provides a good understanding of the direct impact of the pandemic experienced by NICs, but it also has several limitations. The most important one is that we were only able to include 18 NICs from 14 countries in our survey. A larger and more diverse pool of NICs would be needed to make any definitive statements about the global impact the pandemic has had on national influenza systems. A second limitation is that the NICs only filled out the questionnaire at one moment in time, yet results are likely to have changed over the course of the pandemic. In order to closely monitor and collect contextspecific information, regular surveys should be carried out. Lastly, some questions, regarding increases in "robustness" or "structural" changes left room for interpretation for the respondent of the questionnaire. However, respondents indicating that they had indeed seen structural changes to the surveillance system or found their system to be more robust were invited to motivate their answer in a free text box (which all respondents made use of).

| CONCLUSION
The SARS-CoV-2 pandemic has had a substantial impact on both the circulation of influenza and the performance of the global WHO influenza surveillance system between January 2020 and March 2022.

DATA AVAILABILITY STATEMENT
Data collected as part of this study is treated confidentially, and as such has not been made available. Anonymized results can be shared upon request.

PEER REVIEW
The peer review history for this article is available at https://www.